The morbidity and mortality associated with essential hypertension have strained our nation with loss of manpower and with high cost of health care. Utilizing established radioimmunoassays, we found that plasma bradykinin in normal individuals is sensitive to the state of sodium balance, saline infusion and postural change. In addition, bradykinin in response to these manipulations responded in a parallel manner similar to that observed in plasma renin activity, angiotensin II and aldosterone, suggesting a close physiologic interrelationship between these hormones. We found also that urinary kallikrein excretion is diminished in patients with essential hypertension and it varied inversely with the state of sodium-balance. The objectives of the proposed study are to examine: (a) the kinetics of the kinin system and postural alteration in normal and hypertensive persons; (b) the possible role of kinins in blood pressure regulation and in the pathogenesis of primary (or essential) and secondary hypertension; (c) the interrelationship between the kallikrein-kinin and renin-angiotensin systems since they responded to acute and chronic changes in sodium balance in normal individuals and the effector hormones of these two systems are potent vasoactive substances with directly opposite actions on the blood vessels; (d) test the concept of biosystems approach, involving the renin-angiotensin and kallikrein-kinin systems in the study of hypertension and other diseases. It is hoped the information gained from the proposed studies will lead to a better insight into the pathogenesis of essential hypertension, and its treatment. Conditions with abnormal kinin or renin-angiotensin systems are included in our study. Included in this application is the proposal to examine the possible physiologic role of bradykinin in normal regulation of renal function.